This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. UT Southwestern Medical Center at Dallas has assembled four teams to focus on a major medical problem in the U.S. - obesity and the metabolic syndrome. This project has created mechanisms to bring together diverse groups of investigators to investigate the behavioral, metabolic, and molecular events that cause obesity and the metabolic syndrome. The major focus of this effort will be on the brain and liver, organs that both play central roles in the development of obesity and its adverse metabolic consequences. Our goals are to better understand how the brain regulates food intake and energy expenditure and to reveal how dysregulation of glucose and lipid metabolism in the liver contributes to the development of the metabolic syndrome. To address these objectives, we have developed four research teams that vary in approaches and expertise that will interact extensively to pursue the shared goals of this project. Collaborations among investigators will occur on two levels. Within each team, extensive exchanges between investigators will foster direct collaborative efforts. Interactions will also occur between the four major teams to capitalize on the diverse expertise within each of the four groups and to provide comprehensive approaches to our major objectives. These four teams are: Team 1: Central Regulators of Energy Metabolism (Lead Investigator, Keith Parker); Team 2: Molecular Biology of Energy Metabolism (Lead Investigator, Jay D. Horton);Team 3: In Vivo Intermediary Metabolism (Lead Investigator, Craig Malloy) and Team 4: Human Genetics and Energy Metabolism (Lead Investigator, Scott Grundy). Over the next three years, the major objectives will be to: 1) develop a program to foster interdisciplinary interactions at UT Southwestern to study obesity and the metabolic syndrome;2) develop a state-of-the-art program to elucidate the metabolic and molecular basis of obesity and the metabolic syndrome using genetically modified mice;and 3) support the translation of scientific findings made in animal models to humans. This study uses the Research Resource for the 2H and 13C NMR of plasma samples from humans. It is classified here as a service project because the actual use of the spectrometers is directed by Dr. Jeff Browning.